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Acta Gastro-enterologica Belgica Dec 2013Mixed cryoglobulinemia (MC) is an important complication of hepatitis C virus (HCV) infection. Antiviral therapy is now an important approach for symptomatic HCV-MC;... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Mixed cryoglobulinemia (MC) is an important complication of hepatitis C virus (HCV) infection. Antiviral therapy is now an important approach for symptomatic HCV-MC; some information exists on IFN mono-therapy for symptomatic HCV-MC in the non-transplant setting, but its efficacy is still unclear.
METHODS
We evaluated efficacy and safety of mono-therapy with standard or pegylated interferon (IFN) for symptomatic HCV-associated MC in non-immunosuppressed individuals by performing a systematic review of the literature with a meta-analysis of clinical studies. We used the random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The primary outcome was sustained viral response (SVR, as a measure of efficacy), and the secondary outcome was the drop-out rate due to side-effects (as a measure of tolerability).
RESULTS
We identified eleven clinical studies (n = 235 unique patients) ; the rate of baseline kidney involvement ranged between 11% and 74%. The summary estimate of frequency of sustained viral response was 0.15 with a 95% Confidence Interval (CI) of 0.08; 0.22 (random-effects model). Significant heterogeneity occurred (P= 0.001; Chi= 28.9%). Stratified analysis did not meaningfully change the results. The frequency of patients stopping antiviral agents was 3.4% ; most patients experienced minor side effects which did not require interruption of therapy. Baseline cirrhosis (P <0.04), kidney involvement (P <0.07), and arthralgias (P <0.04) showed negative impact on viral response. We found an excellent relationship between viral and clinical response [weighted K = 0.72 (95% CI, 0.54; 0.89)], by an evaluation at individual level on a subset of reports (n = 65 unique patients).
CONCLUSIONS
This meta-analysis of clinical studies shows that antiviral therapy with standard or pegylated IFN alone for symptomatic MC associated with HCV gives satisfactory response in a minority of patients only. Clinical trials based on combination therapy (pegylated interferon plus ribavirin) or novel immunosuppressive agents are under way in order to improve efficacy and safety of symptomatic HCV-MC. ,
Topics: Clinical Trials as Topic; Cryoglobulinemia; DNA, Viral; Hepacivirus; Hepatitis C, Chronic; Humans; Immunologic Factors; Interferon-alpha
PubMed: 24592538
DOI: No ID Found -
Clinical Infectious Diseases : An... Sep 2015Achievement of a sustained virologic response (SVR) after treatment for Hepatitis C infection is associated with improved outcomes. This meta-analysis aimed to determine... (Meta-Analysis)
Meta-Analysis Review
Long-Term Treatment Outcomes of Patients Infected With Hepatitis C Virus: A Systematic Review and Meta-analysis of the Survival Benefit of Achieving a Sustained Virological Response.
BACKGROUND
Achievement of a sustained virologic response (SVR) after treatment for Hepatitis C infection is associated with improved outcomes. This meta-analysis aimed to determine the impact of SVR on long-term mortality risk compared with nonresponders in a range of populations.
METHODS
An electronic search identified all studies assessing all-cause mortality in SVR and non-SVR patients. Eligible articles were stratified into general, cirrhotic, and populations coinfected with human immunodeficiency virus. The adjusted hazard ratio (95% confidence interval [CI]) for mortality in patients achieving SVR vs non-SVR, and pooled estimates for the 5-year mortality in each group were calculated.
RESULTS
31 studies (n = 33 360) were identified as suitable for inclusion. Median follow-up time was 5.4 years (interquartile range, 4.9-7.5) across all studies. The adjusted hazard ratio of mortality for patients achieving SVR vs non-SVR was 0.50 (95% CI, .37-.67) in the general population, 0.26 (95% CI, .18-.74) in the cirrhotic group, and 0.21 (.10-.45) in the coinfected group. The pooled 5-year mortality rates were significantly lower for patients achieving SVR compared with non-SVR in all 3 populations.
CONCLUSIONS
The results suggest that there is a significant survival benefit of achieving an SVR compared with unsuccessful treatment in a range of populations infected with hepatitis C virus.
Topics: Adolescent; Adult; Aged; Antiviral Agents; Hepacivirus; Hepatitis C, Chronic; Humans; Middle Aged; Young Adult
PubMed: 25987643
DOI: 10.1093/cid/civ396 -
The International Journal on Drug Policy Oct 2021We performed a systematic review and meta-analysis addressing community-based assessment and treatment of hepatitis C virus (HCV)-related liver disease, injecting drug... (Meta-Analysis)
Meta-Analysis Review
Community-Based Assessment and Treatment of Hepatitis C Virus-Related Liver Disease, Injecting Drug and Alcohol Use Amongst People Who Are Homeless: A Systematic Review and Meta-Analysis.
BACKGROUND/AIMS
We performed a systematic review and meta-analysis addressing community-based assessment and treatment of hepatitis C virus (HCV)-related liver disease, injecting drug use (IDU) and alcohol use amongst people who are homeless (PWAH).
METHODS
Using systematic review methodology, databases were searched (MEDLINE/EMBASE/CINAHL) for studies combining PWAH, HCV-related liver disease and community assessment until December 2019. Studies with a sample size ≥ 30, with PWAH constituting at least 30% of the cohort were included and a quality assessment performed. Pooled estimates of key indicators were analysed using meta-analysis.
RESULTS
We identified 39 studies (n = 13,918), 37 categorised as poor quality (Newcastle-Ottawa Scale). Prevalence of homelessness ranged between 30%-100% (37 studies). Eight studies provided all of the following: HCV screening, alcohol/substance use/liver fibrosis assessment and HCV treatment. No study provided interventions for alcohol use, with two providing opioid substitution treatment. Alcohol use prevalence (24 studies) was 4%-97%, being 59% (95% CI 20%-92%) in four studies that included only PWAH. Recent IDU prevalence (16 studies) was 7%-73%, being 21% (95% CI 17%-26%) in four studies that included only PWAH. HCV seroprevalence (25 studies) was 2.5% - 58%; in 13 studies that included only PWAH, this was 20% (95% CI 12%-30%). Prevalence of F4 fibrosis (nine studies) was 6%-28%, being 7% and 16% in two studies that included only PWAH. Direct acting antiviral-based intention-to-treat sustained virological response (SVR) rates (five studies) were 82%-92%, being 92% in the one study that included only PWAH. In the only two randomised controlled trials (RCT) identified, community-based interventions (mental health/peer mentor) significantly increased linkage to care (p = 0.04), HCV treatment (p = 0.005) and SVR rates (p = 0.018).
CONCLUSION
The burden from alcohol/IDU and HCV, and consequently liver disease in PWAH needs addressing. RCT trials assessing community-based interventions to improve liver health in PWAH are needed.
Topics: Antiviral Agents; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Ill-Housed Persons; Humans; Liver; Pharmaceutical Preparations
PubMed: 34210551
DOI: 10.1016/j.drugpo.2021.103342 -
Clinical Infectious Diseases : An... Apr 2013A systematic review and meta-analysis were conducted to examine the efficacy and safety of pegylated interferon (peg-IFN) alfa-2a and peg-IFN alfa-2b plus ribavirin... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of pegylated interferon alfa-2a or alfa-2b plus ribavirin for the treatment of chronic hepatitis C in children and adolescents: a systematic review and meta-analysis.
BACKGROUND
A systematic review and meta-analysis were conducted to examine the efficacy and safety of pegylated interferon (peg-IFN) alfa-2a and peg-IFN alfa-2b plus ribavirin (RBV) in children and adolescents with chronic hepatitis C virus (HCV).
METHODS
Medline, Embase, and Cochrane Central Register of Controlled Trials were searched. Clinical trials examining peg-IFN alfa-2a or peg-IFN alfa-2b plus RBV among persons ages 3-18 years with HCV were included. Data were abstracted for complete early virologic response (EVR), sustained virologic response (SVR), relapse, treatment discontinuations, hematologic and dermatologic adverse events, and growth inhibition.
RESULTS
Eight trials met the inclusion criteria. Results indicate that 70% of subjects (95% confidence interval [CI], 58%-81%) achieved EVR, and 58% (95% CI, 53%-64%) achieved SVR. EVR and SVR were higher for those with HCV genotypes 2/3 than 1/4. Discontinuation due to adverse events and discontinuation due to viral breakthrough were each 4%, discontinuation due to a lack of response was 15%, and relapse was 7%. Anemia, neutropenia, leukopenia, and thrombcytopenia were 11%, 32%, 52%, and 5%, respectively. Alopecia, injection site erythema, and pruritus were 13%, 27%, and 10%, respectively. Small growth inhibitions were observed during treatment.
CONCLUSION
The results of this meta-analysis indicate that peg-IFN/RBV combination treatment is effective and safe in treating children and adolescents with HCV.
Topics: Adolescent; Antiviral Agents; Child; Child, Preschool; Clinical Trials as Topic; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Hepatitis C, Chronic; Humans; Interferon-alpha; Polyethylene Glycols; Recombinant Proteins; Ribavirin; Treatment Outcome
PubMed: 23243171
DOI: 10.1093/cid/cis1031 -
PloS One 2022Efforts are ongoing by researchers globally to develop new drugs or repurpose existing ones for treating COVID-19. Thus, this led to the use of oseltamivir, an antiviral... (Meta-Analysis)
Meta-Analysis
Efforts are ongoing by researchers globally to develop new drugs or repurpose existing ones for treating COVID-19. Thus, this led to the use of oseltamivir, an antiviral drug used for treating influenza A and B viruses, as a trial drug for COVID-19. However, available evidence from clinical studies has shown conflicting results on the effectiveness of oseltamivir in COVID-19 treatment. Therefore, this systematic review and meta-analysis was performed to assess the clinical safety and efficacy of oseltamivir for treating COVID-19. The study was conducted according to the PRISMA guidelines, and the priori protocol was registered in PROSPERO (CRD42021270821). Five databases were searched, the identified records were screened, and followed by the extraction of relevant data. Eight observational studies from four Asian countries were included. A random-effects model was used to pool odds ratios (ORs), mean differences (MD), and their 95% confidence intervals (CI) for the study analysis. Survival was not significantly different between all categories of oseltamivir and the comparison groups analysed. The duration of hospitalisation was significantly shorter in the oseltamivir group following sensitivity analysis (MD -5.95, 95% CI -9.91--1.99 p = 0.003, heterogeneity I2 0%, p = 0.37). The virological, laboratory and radiological response rates were all not in favour of oseltamivir. However, the electrocardiographic safety parameters were found to be better in the oseltamivir group. However, more studies are needed to establish robust evidence on the effectiveness or otherwise of oseltamivir usage for treating COVID-19.
Topics: Humans; Oseltamivir; Antiviral Agents; Influenza, Human; COVID-19 Drug Treatment
PubMed: 36454880
DOI: 10.1371/journal.pone.0277206 -
Reviews in Medical Virology Jan 2022It has been demonstrated that lactoferrin (LF) plays a role in host defence, but evidence on its potential antiviral property from clinical studies is fragmented. Our... (Review)
Review
It has been demonstrated that lactoferrin (LF) plays a role in host defence, but evidence on its potential antiviral property from clinical studies is fragmented. Our systematic review aimed at identifying the effects of orally administered LF against virus infections. The systematic search was conducted on PubMed, Scopus, Web of Science, BioRxiv.org and ClinicalTrials.gov from database inception to 7th January 2021. Eligible articles investigated any virus family and provided data on the effects of orally administered LF of any origin in the prevention and/or management of confirmed viral infections in people of any age. A narrative synthesis of the results was performed. Quality was assessed with the Cochrane Risk-Of-Bias and ROBINS-1 tools. A total of 27 records were included, nine of which were registered protocols. We found data on Flaviviridae (n = 10), Retroviridae (n = 3), Coronaviridae (n = 2), Reoviridae (n = 2) and Caliciviridae (n = 1). Most published trials were at high risk of bias. The findings were heterogeneous across and within viral families regarding virological, immunological and biological response, with no clear conclusion. Some weak but positive results were reported about decrease of symptom severity and duration, or reduction in viral loads. Despite high tolerability, the effects of LF as oral supplement are still inconsistent, both in preventing and managing viral infections. Small sample sizes, variety in recruitment and treatment protocols, and low study quality may have contributed to such heterogeneity. Better-designed studies are needed to further investigate its potential benefits against viral infections, including SARS-CoV-2.
Topics: Anti-Infective Agents; COVID-19; Humans; Lactoferrin; SARS-CoV-2; Virus Diseases
PubMed: 34133812
DOI: 10.1002/rmv.2261 -
The Cochrane Database of Systematic... Jan 2009Waldenstrom's macroglobulinaemia (WM) is an uncommon B-cell lymphoproliferative disorder characterized by bone marrow infiltration and production of monoclonal... (Review)
Review
BACKGROUND
Waldenstrom's macroglobulinaemia (WM) is an uncommon B-cell lymphoproliferative disorder characterized by bone marrow infiltration and production of monoclonal immunoglobulin. Uncertainty remains if alkylating agents, such as chlorambucil, melphalan or cyclophosphamide, are an effective form of management.
OBJECTIVES
To assess the effects and safety of the alkylating agents on Waldenstrom's macroglobulinaemia (WM).
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2008), MEDLINE (1966 to 2008), EMBASE (1980 to 2008), the Chinese Biomedical Base (1982 to 2008) and reference lists of articles.We also handsearched relevant conference proceedings from 1990 to 2008.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing alkylating agents given concomitantly with radiotherapy, splenectomy, plasmapheresis, stem-cell transplantation in patients with a confirmed diagnosis of WM.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials.
MAIN RESULTS
One trial involving 92 participants with pretreated/relapsed WM compared the effect of fludarabine versus the combination of cyclophosphamide (the alkylating agent), doxorubicin and prednisone (CAP). Compared to CAP, the Hazard ratio (HR) for deaths of treatment with fludarabine was estimated to be 1.04, with a standard error of 0.30 (95% CI 0.58 to 1.48) and it indicated that the mean difference of median survival time was -4.00 months, and 16.00 months for response duration. The relative risks (RR) of response rate was 2.80 (95% CI 1.10 to 7.12). There were no statistically difference in overall survival rate and median survival months, while on the basis of response rate and response duration, fludarabine seemed to be superior to CAP for pretreated/relapsed patients with macroglobulinaemia.
AUTHORS' CONCLUSIONS
Although alkylating agents have been used for decades they have never actually been tested in a proper randomised trial. This review demonstrated that there is currently no evidence to suggest that alkylating agents are effective in treating Waldenstrom's macroglobulinaemia.
Topics: Alkylating Agents; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Prednisone; Randomized Controlled Trials as Topic; Vidarabine; Waldenstrom Macroglobulinemia
PubMed: 19160296
DOI: 10.1002/14651858.CD006719.pub3 -
Intervirology 2015We conducted a systematic review and meta-analysis of the influence of host and viral factors on the sustained virologic response (SVR) in hepatitis C virus genotype 6... (Meta-Analysis)
Meta-Analysis Review
Influence of Host and Viral Factors on Patients with Chronic Hepatitis C Virus Genotype 6 Treated with Pegylated Interferon and Ribavirin: A Systematic Review and Meta-Analysis.
OBJECTIVES
We conducted a systematic review and meta-analysis of the influence of host and viral factors on the sustained virologic response (SVR) in hepatitis C virus genotype 6 (HCV-6) patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV).
METHODS
Data were retrieved from Medline, Embase, PubMed and the Cochrane Library for 'genotype 6' studies published up to December 2014 and for abstracts from international scientific meetings. Inclusion criteria were efficacy of PEG-IFN+RBV based on SVR, 24- or 48-week therapy and treatment-naïve patients. Patients with hepatitis B, D and E and HIV coinfection or another concurrent liver disease were excluded. Pooled standard difference, odds ratio and confidence intervals (CIs) were calculated using a random-effect model with STATA 11.
RESULTS
Fourteen studies were included in the meta-analysis. The pooled SVR rate was 80% (95% CI: 0.78-0.83, p < 0.0001; I2 = 71.2%). SVR of the PEG-IFN+RBV-treated HCV-6 patients was markedly higher than that of HCV-1 patients (80.1 vs. 55.3%). The SVR rate was significantly higher for the 48- than the 24-week treatment, but not different among HCV-infected patients with rs12979860 and ss469415590 polymorphisms of the ILFN4 gene (80.6% CC vs. 66.7% non-CC, p = 0.593; 81.1% TT/TT vs. 60% non-TT/TT, p = 0.288). Gender and type of PEG-IFN did not affect SVR rates.
CONCLUSIONS
Treatment outcomes for HCV-6 patients are superior to those for HCV-1 patients and comparable to those of HCV-2 and HCV-3 patients, especially at 48 weeks. The level of fibrosis affects treatment outcome, but SVR rates are not significantly different between genders. IL28B and IFNL4 polymorphisms are not significantly associated with HCV-6 treatment outcome.
Topics: Antiviral Agents; Coinfection; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Immunologic Factors; Interferon-alpha; Polyethylene Glycols; Polymorphism, Genetic; Ribavirin; Treatment Outcome
PubMed: 27010195
DOI: 10.1159/000444366 -
Frontiers in Medicine 2021Hepatitis C virus (HCV)-infected patients treated with direct-acting antivirals (DAAs) are still at risk of developing hepatocellular carcinoma (HCC) after sustained...
Hepatitis C virus (HCV)-infected patients treated with direct-acting antivirals (DAAs) are still at risk of developing hepatocellular carcinoma (HCC) after sustained virologic response (SVR). This study aimed to investigate the role of diabetes mellitus (DM) as a potential predictive risk factor in developing HCC in HCV-infected patients after DAA treatment. This study was registered on PROSPERO under registration number CRD42021230457. We performed a systematic search in four medical databases from inception through November 3rd, 2020. Studies were eligible if they reported on HCV-infected patients treated with DAAs and compared the frequency of HCC in patients with and without DM. We calculated pooled odds ratios, unadjusted (UHR), and adjusted hazard ratios (AHR) with 95% confidence intervals (CIs) in meta-analysis. We included 30 articles in our systematic review and meta-analysis. DM proved to be a significant risk factor of HCC in DAA-treated HCV patients in unadjusted ( = 1.44, CI: 1.15-1.79) and adjusted analyses ( = 1.31, : 1.06-1.62). In the group of patients achieving SVR after DAA therapy, DM increased the risk of HCC in unadjusted ( = 1.3, CI: 1.09-1.51) analysis; however, in adjusted results, the risk was non-significant ( = 1.07, CI: 0.89-1.28). In patients with advanced liver fibrosis, DM was a risk factor for HCC in adjusted ( = 1.36, CI: 1.03-1.8), but not in unadjusted analysis ( = 1.11, CI: 0.8-1.42). DM is an independent risk factor of HCC after DAA treatment in HCV-infected patients. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=230457, identifier: CRD42021230457.
PubMed: 34733865
DOI: 10.3389/fmed.2021.744512 -
Autoimmunity Reviews Aug 2012To review our current knowledge of the pathogenesis of Meniere's disease, including viral infection and immune system-mediated mechanisms, and to discuss the... (Review)
Review
OBJECTIVES
To review our current knowledge of the pathogenesis of Meniere's disease, including viral infection and immune system-mediated mechanisms, and to discuss the pathogenesis as it relates to pharmacotherapy.
SYSTEMATIC REVIEW METHODOLOGY
Relevant publications on the aetiopathogenesis, molecular biology, genetics and histopathology of Meniere's disease from 1861 to 2011 were analysed.
RESULTS AND CONCLUSIONS
Meniere's disease is characterised by intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural pressure. The aetiology and pathogenesis remain unknown. Proposed theories of causation include viral infections and immune system-mediated mechanisms. The immune response in Meniere's disease is focused on inner ear antigens. Approximately one-third of Meniere's disease cases seem to be of an autoimmune origin although the immunological mechanisms involved are not clear. The diagnosis of autoimmune inner ear disease is based either on clinical criteria or on a positive response to steroids. The antiviral approach has virtually eliminated the use of various surgical methods used in the past. Steroid responsiveness is high, and with prompt treatment, inner ear damage may be reversible. The administration of etanercept improves or stabilises symptoms in treated patients. Treatment of antiphospholipid syndrome can be directed toward preventing thromboembolic events by using antithrombotic medications. Only warfarin has been shown to be effective. Gene therapy can be used to transfer genetic material into inner ear cells using viral vectors and to protect, rescue, and even regenerate hair cells of the inner ear.
Topics: Animals; Autoimmune Diseases; Ear, Inner; Humans; Meniere Disease
PubMed: 22306860
DOI: 10.1016/j.autrev.2012.01.004